New Nobel Laureates Speak Out For Increased Research Funding

LUCKY STARS: Harold Kroto was studying carbon clusters when he and coworkers discovered buckyballs. Like many of their predecessors, the winners of the 1996 Nobel Prizes in science have found that the media attention accompanying the honor provides an excellent opportunity to speak out on behalf of important causes. Last month, five of the eight newly named science laureates used their "bully pulpit" to voice concerns about research funding at a National Science Foundation news conference. The five winners-all Americans who have been funded by NSF-expressed fears that the funding sources that made their prize-winning research possible are drying up. The October 17 conference occurred days after the Nobel recipients were announced. In chemistry, three researchers were honored for discoveries that helped establish a new genre of carbon-based materials known as buckminsterfullerenes, or buckyballs. Two immunologists were cited for revealing how T cells methodically attack virus infected cells. Three physicists were tapped to receive the prize for unraveling the complex behavior of superfluidity in helium-3. DOWNSWING: Rice's Robert Curl contends that basic science support is "dismal" compared with 30 years ago. Richard E. Smalley, the Hackerman Professor of Chemistry and a physics professor at Rice University, and Robert F. Curl, Jr., a professor of chemistry at Rice, both lamented the scarcity of science funding in the United States. The pair, along with Sir Harold Kroto, Royal Society Research Professor at the University of Sussex in Brighton, England, were cited for their discovery of buckyballs. These molecules are named for their resemblance to architect R. Buckminster Fuller's geodesic dome design. All three physics winners were on hand at the NSF conference. Stanford University physicists Robert C. Richardson and Douglas D. Osheroff will share their prize with Cornell University physics professor David M. Lee for their work in elucidating the superfluid nature of helium-3. The trio expressed their concerns about the lack of innovation and corporate support for research. REVELATION: Zurich's Rolf Zinkernagel believes his work helped scientists understand cell-mediated immunity. In physiology or medicine, Peter C. Doherty of St. Jude's Children's Research Hospital in Memphis, Tenn., and Rolf M. Zinkernagel of the University of Zurich, Switzerland, were named to receive the prize for their groundbreaking explanations of the immune system's antiviral defenses. The pair were not at the NSF conference. Doherty, chairman of St. Jude's department of immunology, and Zinkernagel, professor and director of Zurich's Institute of Experimental Immunology, are no strangers to prestigious awards: Each won an Albert Lasker Medical Research Award last year for their work (N. Sankaran, The Scientist, Oct. 16, 1995, page 1). In addition, they both received a Gairdner Foundation International Award in 1986. OPEN DOOR: St. Jude's Peter Doherty sees a wide range of potential anti-tumor vaccines stemming from the Nobel work. Each newly named Nobel laureate will share a prize of $1.12 million, the largest ever. The Nobels will be presented next month in Stockholm, Sweden. At the NSF conference, the researchers decried what they see as a lack of commitment to basic science on the part of both the federal government and industry. "The state of basic science is dismal compared to 30 years ago," said Curl, 63, at the conference. "American industry is getting away from basic, long-term research, and instead emphasizing applied, shortterm profit. It's a problem for academic scientists because the universities have low turnover, and it's frustrating for the best graduate students to get opportunities." Osheroff, who spent 15 years at AT&T Bell Laboratories, lamented the demise of industry labs in order to boost the bottom line. The 51-year old J.G. Jackson and C.J. Wood Professor of Physics at Stanford contends that profit is frequently emphasized to the detriment of research. The reduction in size and scope of the basic research in large industrial laboratories has had a chilling effect on basic science, concurs Lee, 65. "You have to be careful about saying we want more money. We need more investment, but how to do it to help basic research is unclear. Many of the large basic research labs have either closed or significantly reduced their basic research activities." What's more, national laboratories, which supported basic research, are being restructured, he notes. "You need a good basic research program to provide the underpinnings for future discoveries." According to Richardson, the 59-year old Floyd R. Newman Professor of Physics and director of the Laboratory of Atomic and Solid State Physics at Stanford, the lack of federal funding for basic research discourages young people from entering the field. He worries that the sources of innovation will dry up and scientists will concentrate in narrow areas of research. For example, when superconductivity was all the rage, many left certain fields in physics and flocked to superconductivity because that was where the money was, he explained. "People are driven toward conservative, guaranteed results that will be published. Innovation and creativity are destroyed," he adds. New innovations are at hand, however, with the discovery of buckyballs. Many scientists believe that these molecules could spawn a new age of miniaturized electronics, as well as aid in the creation of novel products, including building materials, superconductors, and pharmaceuticals. While researchers had postulated the existence of buckyballs (or fullerenes, short for buckminsterfullerene), Rice's Curl notes that the Nobel-winning discovery of "making symmetrical [soccer ball-shaped] cage molecules out of the chaos of condensing carbon particles was totally surprising. We're still not sure of the mechanism." When Kroto, 57, visited Curl at Rice in 1985, buckyballs were the last thing on his mind. He was studying carbon chains in space-star dust-at the University of Sussex. A chance meeting at a conference led to a collaboration with Curl and Smalley, 53, who were studying semiconductor and metal clusters using equipment that Kroto needed for his experiments. When they went about vaporizing carbon graphite, the chemists found the long chains of carbon atoms that Kroto was looking for. The machine not only produced the chains they expected to find, but also made large amounts of clusters of stable C60 and other cagelike molecules. "When we saw C60 we were excited-and bowled over by its beauty," Kroto recalls. The scientists subsequently worked out the intricate atomic patterns of hexagons and pentagons necessary for the buckyball shape. Along with graduate students Jim Heath and Sean O'Brien, the researchers found they could produce stable carbon-60 and carbon-70 molecules. The Nobel-winning research was reported in a paper entitled "C60: Buckminsterfullerene" (H.W. Kroto et al., Nature, 318:162-3, 1985). However, according to a Nature report (D. Swinbanks, 383:562, 1996), the existence of a C60 molecule was postulated 15 years earlier in a paper by Eiji Osawa, a Japanese chemist then at Kyoto University. Osawa's paper was published only in Japanese, and Japanese researchers were uninterested in his work. Kroto, who did not know of Osawa's paper at the time because of the language barrier, has since credited the Asian researcher, who is now at Toyohashi University of Technology. COOKING: Arizona's Donald Huffman and colleague Wolfgang Krätschmer found a way to make large amounts of buckyballs. After their discovery, fullerenes remained a laboratory phenomenon. Only small amounts could be produced. Not until Donald Huffman, now Regents Professor of Physics at the University of Arizona in Tucson, and colleague Wolfgang Krätschmer of the Max Planck Institute for Nuclear Physics in Heidelberg, Germany, found a way to make large amounts of buckyballs was the field poised to take off. "Had there not been a method to make it in measurable amounts, it would not have had an impact," notes Smalley. Curl also acknowledges Huffman's research. "We had lots of evidence prior to 1990 about the existence of fullerenes, and [Huffman's] group's paper in 1990 (W. KrStschmer et al., Nature, 347:354-8) got this into the hands of chemists," he says. "Huffman's work took it from mass spectrometers to the laboratory. It must have been a close decision by the Nobel committee over who should get it." Many had thought that those involved in the fullerene discoveries would win the Nobel, but no one was quite sure when it would be awarded or who would actually win it. In fact, when the Royal Swedish Academy of Sciences announced the chemistry winners, the University of Arizona press office issued a news release touting Huffman's work as equally deserving of the award. "It's still premature to know what the work will be good for," says Huffman, who notes that the winners are deserving of their award. "There have been probably 100 patent applications filed for their [fullerenes'] uses." BULLISH: Richard Smalley of Rice is excited about the potential of buckyballs: "The impact could be vast." Smalley-who received a John Scott Award from the city of Philadelphia in 1993 for his work (C. Montesano, The Scientist, Dec. 13, 1993, page 22)-is bullish on the future of buckyballs. "Within the last year, we have realized that carbon has a genius for making tubes, called armchair tubes, in which the ends are cut open. These tubes are predicted to be the strongest fibers that exist, hundreds of times stronger than steel," he explains. "The carbon cage in C60 is robust; it has a rich chemistry to which you can attach any molecule. That makes it great-you can connect it to the rest of chemistry. "The impact could be vast," he believes. "Because they are made of carbon, we will have a new class of molecules whose systematic chemistry will become a major activity of chemists. These are the first molecules we've ever had that are truly metallic in nature. Molecular electronics-nanoelectronics-may be possible." In helping explain how the immune system's T cells fend off viruses two decades ago, researchers Doherty and Zinkernagel not only impacted but also revolutionized the field of immunology. Their findings opened up the potential for developing vaccines for cancer and other disorders. Doherty, 55, is excited about the "whole new world of possibilities to develop T-cell peptide vaccines for infections, possibly tumors, as well as T-cell therapy for tumors." Yet Doherty and Zinkernagel didn't start out seeking an explanation for T-cell behavior. In fact, they were thrown together in the same lab owing to a lack of space at the John Curtin School of Medical Research in Canberra, Australia, in the early 1970s. They paired up to try to figure out the role of T cells in destroying virus-infected brain cells of mice infected with lymphocytic choriomeningitis virus (LCMV). Their discovery in 1974 helped explain how the immune system's T cells recognize their targets, providing a simple explanation of a key part of how T cells fight off viruses: They distinguish between virus-infected and normal cells. The scientists also found that T cells recognize certain cell proteins, called histocompatibility antigens. These antigens, products of the genes in the major histocompatibility complex (MHC), are unique for each individual. They were known to trigger transplant rejection, but not much else. In the course of their experiments, the researchers discovered that it wasn't the virus that was killing cells in disease; rather, it was the immune system's own T cells. They showed that the immune cells of one mouse strain wouldn't destroy infected cells of a second strain because the MHC proteins differed. Says the 52-year-old Zinkernagel: "[The work] gave a reasonable explanation for the existence of transplantation antigens, and opened up a number of other areas for study, including T cell recognition and MHC-disease linkages. It has changed the thinking of how cell mediated immunity works." "What took longer to be accepted was our interpretation of the findings," notes Doherty, who today is studying immunological memory with mouse models of influenza and Epstein-Barr virus. When the pair made the discovery, "no one had thought that the T cell focused on the virus-infected cell surface," he recalls. "It took another decade for the field to accept that a single T cell receptor was responsible." The work was detailed in a paper entitled "Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system" (R.M. Zinkernagel, P.C. Doherty, Nature, 248:701-2, 1974). A paper entitled "Immunological surveillance against altered self components by sensitized T lymphocytes in lymphocytic choriomeningitis" (R.M. Zinkernagel, P.C. Doherty, Nature, 251:547-8, 1974) reported further research. Immunologist Georgio Trinchieri terms Doherty and Zinkernagel's work "a simple observation, yet it revolutionized how the immune system and the T lymphocyte are understood, particularly in our understanding of T-cell recognition of viruses." Trinchieri, a professor at the Wistar Institute of Anatomy and Biology in Philadelphia, knew Doherty when he was a professor at Wistar in the late 1970s and early 1980s. Philippa Marrack, a Howard Hughes Medical Institute investigator at the National Jewish Center (formerly the National Jewish Center for Immunology and Respiratory Medicine) in Denver, says, "This discovery led to something most already believe: that something about the way the T cells recognize our own peptides bound to MHC molecules causes that predisposition. The way that an antigen is recognized by T cells [that] have that particular MHC molecule makes that person more likely to get a particular autoimmune disease. Knowledge of this fact will help people develop vaccines for cancer, for example." While the work from the immunology winners opens doors to the future, the research on the isotope helium-3 by the prize winning physics team may have shed light our past, providing a possible description of the first moments of the universe. As helium becomes superfluid and flows without resistance, the transitions that occur are like those processes believed to have taken place a fraction of a second after the Big Bang. CONCERNED: Stanford's Donald Osheroff worries that industry's emphasis on the bottom line will hinder basic research. For Osheroff, April 20, 1972, when he was a graduate student in physics at Cornell, was a special morning. His discovery of superfluidity at 2:40 a.m.-"when I knew something that no one knew"-was a moment he ranks as even better than getting a call from the Nobel committee 24 years later. A TOAST: From left, Cornell's David Lee and Robert Richardson celebrate their Nobel Prize. Both are concerned that U.S. research funding sources will dry up. What Osheroff and his advisers, Richardson and Lee, had discovered was that helium-3 can be made a superfluid at about two-thousandths of a degree above absolute zero. The discovery "transformed the direction of theoretical and experimental research in low temperature physics," wrote N. David Mermin, the Horace White Professor of Physics at Cornell, in a 1988 letter to the Nobel Committee for Physics in which he nominated the group. "It was a completely beautiful thing because it was unexpected," says Richardson. When liquids and solids are cooled toward absolute zero, they sometimes undergo phase transitions and structure changes. Superfluid helium-4, the most common helium isotope, has been a common tool of science, enabling scientists to observe quantum effects ordinarily reserved for subatomic particles. Research groups had searched for superfluid helium-3 with little success, until the Cornell team noticed a change in the cooling rate of a sample consisting of both solid and liquid helium-3. Additional measurements showed that the helium-3 had produced two distinct superfluid states. The work appeared in a paper entitled "Evidence for a new phase of solid He-3" (D.D. Osheroff et al., Physical Review Letters, 28:885-8, 1972). "Once helium-3 was discovered, it turned out to be a huge playground," says Lee. "The discovery was somewhat of a surprise. The idea had been around, but we had to pin it down."

New Nobel Laureates Speak Out For Increased Research Funding

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